Interleukin-2 stimulated T lymphocyte cell death for the treatment of autoimmune diseases, allergic responses, and graft rejection

Abstract

A method for the treatment or prevention of autoimmune diseases, allergic or atopic disorders, and graft rejection is provided, comprising inducing the death by apoptosis of a subpopulation of T lymphocytes that is capable of causing such diseases, while leaving substantially unaffected the majority of other T lymphocytes. Cell death is achieved by cycle(s) comprising challenging via immunization these T cells with antigenic substance at short time intervals, or by immunization followed by administering interleukin-2 (IL-2) when these T cells are expressing high levels of IL-2 receptor so as to cause these T cells to undergo apoptosis upon re-immunization with the antigenic peptide or protein. These methods are applicable to the treatment of autoimmune diseases such as, for example, multiple sclerosis, uveitis, arthritis, Type I insulin-dependent diabetes, Hashimoto's thyroiditis, Grave's thyroiditis, autoimmune myocarditis, etc., allergic disorders such as hay fever, extrinsic asthma, or insect bite and sting allergies, food and drug allergies, as well as for the treatment or prevention of graft rejection.

What is claimed: 
     
       1. A method for inhibiting a T cell immune response associated with an autoimmune disease in a human subject, the method comprising repetitively administering to the patient an antigen specifically recognized by T cells, wherein the antigen is administered parenterally to cause the T cells that specifically recognize the antigen to express interleukin-2 (IL-2) or IL-2 receptors, such that the T cell immune response to the antigen is inhibited. 
     
     
       2. The method of claim 1, wherein the autoimmune disease is multiple sclerosis. 
     
     
       3. The method of claim 2, wherein the antigen is myelin basic protein. 
     
     
       4. The method of claim 1, wherein the autoimmune disease is autoimmune uveitis. 
     
     
       5. The method of claim 1, wherein the antigen is administered a about 24 to about 72 hour intervals. 
     
     
       6. The method of claim 1, wherein the antigen is a peptide. 
     
     
       7. The method of claim 6, wherein the peptide is administered at a dose between about 10 to about 1000 μg. 
     
     
       8. The method of claim 1, further comprising administering interleukin-2. 
     
     
       9. The method of claim 8, wherein the interleukin-2 is administered about 12 to about 72 hours after the antigen is administered. 
     
     
       10. The method of claim 8, wherein the interleukin-2 is administered parenterally. 
     
     
       11. A method for eliminating a subpopulation of T cells associated with an autoimmune disease in a sample, the method comprising contacting the sample with interleukin-2, followed by stimulation of the T cells. 
     
     
       12. The method of claim 11, wherein the step of stimulating the T cells is carried out by contacting the sample with an antigen recognized by the T cells. 
     
     
       13. The method of claim 11, wherein the autoimmune disease is multiple sclerosis. 
     
     
       14. The method of claim 1, wherein the antigen is administered at 2 to 3 day intervals.